Hyperpolarized liquid-phase contrast media can enhance the sensitivity of MRI by a factor of 10,000 or more. These signal enhancements may yield significant improvements in many existing applications of MRI, including angiography and perfusion imaging. In addition, because it is possible to polarize endogenous substances, these techniques are beginning to show promise for new applications such as `real-time' metabolic imaging that monitors not just transport and uptake of agents, but metabolic transformations as well. The gains in sensitivity afforded by hyperpolarization are offset to some degree by the relatively short lifetime of the signal enhancement. Indeed, once an agent has been prepared, its magnetization decays away irreversibly at a rate dictated by the spin-lattice relaxation time T1. Existing agents generally have relaxation times on the order of a minute or less, implying that the hyperpolarized magnetization has a useful lifetime of a few minutes. These short lifetimes limit the time window that is available transport, uptake, and metabolism of the agents. This, in turn, may limit the range of feasible applications for hyperpolarized MRI. Recent work has shown that certain coherent quantum-mechanical spin states can have lifetimes nearly an order of magnitude longer than the conventional T1 relaxation time. Moreover, these long-lived states are analogous to states employed in parahydrogen-induced polarization, one of the common methods for preparing hyperpolarized media. In our proposed research, we will investigate the possibility of applying parahydrogen-induced polarization and related methods to prepare long-lived hyperpolarized states. Preliminary experimental results on hyperpolarized protons have already demonstrated states with lifetimes 2.5 times longer than the conventional T1 relaxation time, and examples of 8-fold enhancements have been documented in the literature. We have also begun theoretical work to determine the origin of these enhanced lifetimes. If similar enhancements can be obtained in systems containing nuclei such as Carbon-13 that have long relaxation times when isolated from protons, then scaling arguments suggest that it may be possible to prepare hyperpolarized agents with lifetimes of 10 minutes or more. This, in turn, may enable a much wider range of applications for hyperpolarized MRI. We propose a series of theoretical calculations and experimental studies that will identify promising agents for long-lived proton systems. In addition, we will develop methods for preparing candidate long-lived states in systems containing nuclei such as Carbon-13. The lifetimes of these agents will be measured in vitro and compared with theory, and in vivo measurements will be performed in animals. PUBLIC HEALTH RELEVANCE: Hyperpolarized liquid contrast media can enhance the sensitivity of magnetic resonance imaging (MRI) by a factor of 10,000 relative to conventional methods. Many potential applications of hyperpolarization are limited by the short lifetime of the signal enhancement, which is generally on the order of a few minutes. In our proposed work, we will investigate methods for achieving longer lifetimes through the use of specially prepared quantum-mechanical spin states. Theoretical and experimental work will be used to develop an understanding the mechanisms that enable prolonged lifetimes, and candidate contrast agents will be identified and tested. [unreadable] [unreadable] [unreadable]